The objective of this proposal is to evaluate the influence of the hypothalamus upon pancreatic islet mass, body weight and insulin secretion. Female Wistar rats will be used as the animal model. Stereotaxic lesions of the ventromedial hypothalamus (VMH) and/or vagotomy shall be performed to alter the sympathetic and parasympathetic neural inputs of the endocrine pancreas. Rats will be studied in the presence or absence of obesity to separate the influence of neural signals from that of body weight in the control of islet mass and function. Quantitative morphologic techniques such as stereology and autoradiography will be used to evaluate the alterations of islet cytology and mass induced by VMH lesions and/or vagotomy. Physiologic studies utilizing radioimmunoassays and extraction techniques will be performed to determine changes of insulin secretion, glucose tolerance and islet hormone stores following experimental manipulations. Because the number of somatostatin-containing D cells is increased in diabetes mellitus, special attention will be directed toward defining the changes of this islet cell population following VMH lesions and/or vagotomy. The specific goals of this research are to define the precise cytologic bases for alterations of islet size known to occur after VMH lesions and/or vagotomy and to correlate these anatomic changes with those of endocrine pacreatic function.